KETOMETHYLENE AND METHYLENEAMINO PSEUDOPEPTIDE ANALOGS OF INSECT ALLATOSTATINS INHIBIT JUVENILE-HORMONE AND VITELLOGENIN PRODUCTION IN THE COCKROACH BLATTELLA-GERMANICA

Metabolic studies on insect allatostatins have suggested that the dipe ptide Leu-Tyr may be a target for endopeptidases. In order to increase resistance to degradation, methyleneamino Psi[CH2NH] and ketomethylen e Psi[COCH2] peptide bond surrogates have been introduced at the posit ion Leu(3)-Tyr(4) of the allatostatin Asp-Arg-Leu-Tyr-Ser-Phe-Gly-Leu- amide (BLAST-2), and Leu(3)-Phe(4) of [Phe(4)]BLAST-2, respectively. A ssays of inhibition of juvenile hormone (JH) synthesis in vitro by cor pora allata from the cockroach Blattella germanica showed that both an alogues were similarly active to the respective model peptides. The me thyleneamino analogue was further tested in vivo as an inhibitor of JH synthesis, and in vivo and in vitro as an inhibitor of vitellogenin p roduction by the fat body of B. germanica. The analogue was less activ e than BLAST-2 when tested in vitro, but more active than it when test ed in vivo. (C) 1997 Elsevier Science Ltd. All rights reserved.